A severe but reversible reduction in insulin sensitivity is observed in patients with insulinoma

Furnica, Raluca Maria; Istasse, L.; Maiter, Dominique

doi:10.1016/j.ando.2017.08.001

Cited by 10 publications

(9 citation statements)

References 32 publications

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“…Increased plasma insulin levels (hyperinsulinemia) develop to counterbalance initial peripheral insulin resistance, but strong evidence indicate that this contributes to and exacerbates insulin resistance [11,55]. Patients with insulinoma that exhibit significantly elevated blood insulin levels have insulin resistance [63].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, evidence from in vivo animal studies indicates that elevation of insulin levels by exogenous insulin administration results in insulin resistance [11,52,53]. Additionally, patients with primary insulinoma and no prior medical history of metabolic syndrome acquired insulin resistance, and complete resection of the insulinoma restored normal glucose metabolism and insulin sensitivity [54,55]. In obese individuals without T2DM, insulin hypersecretion and hyperinsulinemia are more prevalent than insulin resistance, indicating that hyperinsulinemia may precede and/or exacerbate insulin resistance [56,57].…”

Section: Introductionmentioning

confidence: 99%

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Amelioration of High-Insulin-Induced Skeletal Muscle Cell Insulin Resistance by Resveratrol Is Linked to Activation of AMPK and Restoration of GLUT4 Translocation

et al. 2020

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Insulin resistance, the hallmark of type 2 diabetes mellitus (T2DM), is linked to hyperinsulinemia, which develops to counterbalance initial peripheral hormone resistance. Studies indicate that chronically elevated levels of insulin lead to skeletal muscle insulin resistance by deregulating steps within the insulin signaling cascade. The polyphenol resveratrol (RSV) has been shown to have antidiabetic properties in vitro and in vivo. In the present study, we examined the effect of RSV on high insulin (HI)-induced insulin resistance in skeletal muscle cells in vitro and investigated the mechanisms involved. Parental and GLUT4myc-overexpressing L6 rat skeletal muscle cells were used. [3H]2-deoxyglucose (2DG) uptake was measured, and total and phosphorylated levels of specific proteins were examined by immunoblotting. Exposure of L6 cells to HI levels (100 nM) for 24 h decreased the acute-insulin-stimulated 2DG uptake, indicating insulin resistance. HI increased ser307 and ser636/639 phosphorylation of IRS-1 (to 184% ± 12% and 225% ± 28.9% of control, with p < 0.001 and p < 0.01, respectively) and increased the phosphorylation levels of mTOR (174% ± 6.7% of control, p < 0.01) and p70 S6K (228% ± 33.5% of control, p < 0.01). Treatment with RSV abolished these HI-induced responses. Furthermore, RSV increased the activation of AMPK and restored the insulin-mediated increase in plasma membrane GLUT4 glucose transporter levels. These data suggest that RSV has a potential to counteract the HI-induced muscle insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Amelioration of High-Insulin-Induced Skeletal Muscle Cell Insulin Resistance by Resveratrol Is Linked to Activation of AMPK and Restoration of GLUT4 Translocation

et al. 2020

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“…Furthermore, Bar and colleagues also observed reduced insulin activity at its receptor in a case of insulinoma 34 . Intriguingly, insulin resistance in insulinoma cases has been reversed after surgical resection 32,33 . Although it is presumed that insulin resistance in cases of insulinoma functions primarily to maintain normal blood glucose levels, its pathophysiological significance remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…28,29 Consequently, hypoglycemic symptoms may be attenuated during pregnancy in patients with insulinoma. Interestingly, previous reports noted insulin resistance in patients with insulinoma, [30][31][32][33] despite the manifestation of hypoglycemic symptoms. Furthermore, Bar and colleagues also observed reduced insulin activity at its receptor in a case of insulinoma.…”

Section: T a B L E 2 Prolonged Supervised Fasting Testmentioning

confidence: 96%

A case of insulinoma diagnosed postpartum with hypoglycemic symptoms that were masked during pregnancy

Abe

Takeda

Takiyama

et al. 2021

Clinical Case Reports

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“…Hence, insulin presents a double-edged agent, being required for controlling hyperglycemia while concomitantly promoting resistance to insulin in the glycemic context [178]. Indeed, insulinoma patients are resistant to insulin and recover to normal sensitivity upon tumor resection [179]. In line with that, the percentage of T2D patients who reach an HbA1C target <7.0% progressively decrease with advancing anti-diabetic treatments, amounting to 88% and 36% in patients treated with metformin only or with a variety of antidiabetic drugs including insulin, respectively [27].…”

Section: Mtorc1-centric Vs Gluco-centric Paradigm Of T2dmentioning

confidence: 99%

Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm

Bar‐Tana

2020

Rev Endocr Metab Disord

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The current paradigm of type 2 diabetes (T2D) is gluco-centric, being exclusively categorized by glycemic characteristics. The gluco-centric paradigm views hyperglycemia as the primary target, being driven by resistance to insulin combined with progressive beta cells failure, and considers glycemic control its ultimate treatment goal. Most importantly, the gluco-centric paradigm considers the non-glycemic diseases associated with T2D, e.g., obesity, dyslipidemia, hypertension, macrovascular disease, microvascular disease and fatty liver as 'risk factors' and/or 'outcomes' and/or 'comorbidities', rather than primary inherent disease aspects of T2D. That is in spite of their high prevalence (60-90%) and major role in profiling T2D morbidity and mortality. Moreover, the gluco-centric paradigm fails to realize that the non-glycemic diseases of T2D are driven by insulin and, except for glycemic control, response to insulin in T2D is essentially the rule rather than the exception. Failure of the glucocentric paradigm to offer an exhaustive unifying view of the glycemic and non-glycemic diseases of T2D may have contributed to T2D being still an unmet need. An mTORC1-centric paradigm maintains that hyperactive mTORC1 drives the glycemic and non-glycemic disease aspects of T2D. Hyperactive mTORC1 is proposed to act as double-edged agent, namely, to interfere with glycemic control by disrupting the insulin receptor-Akt transduction pathway, while concomitantly driving the non-glycemic diseases of T2D. The mTORC1-centric paradigm may offer a novel perspective for T2D in terms of pathogenesis, clinical focus and treatment strategy.

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A severe but reversible reduction in insulin sensitivity is observed in patients with insulinoma

Cited by 10 publications

References 32 publications

Amelioration of High-Insulin-Induced Skeletal Muscle Cell Insulin Resistance by Resveratrol Is Linked to Activation of AMPK and Restoration of GLUT4 Translocation

Amelioration of High-Insulin-Induced Skeletal Muscle Cell Insulin Resistance by Resveratrol Is Linked to Activation of AMPK and Restoration of GLUT4 Translocation

A case of insulinoma diagnosed postpartum with hypoglycemic symptoms that were masked during pregnancy

Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm

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